The pathobiology of hematopoiesis can be studied by examining disease states of known etiology which often manifest pancytopenia. Hematological abnormalities, including leukopenia, anemia, bone marrow dysplasia, and thrombocytopenia are frequent in patients with AIDS, a disorder due to HTLV-III/LAV infection. Although the primary target cell of infection appears to be the T4 lymphocyte, infection of other cell types, particularly bone marrow progenitors and macrophages, has not been fully explored. The synthesis of hematopoietic growth factors by monocyte-macrophages and T cells, as well as the importance of these cells in animal lentivirus infections, provides a model for studying suppression of hematopoiesis. Preliminary data demonstrate infection of macrophages by HTLV-III/LAV in vitro and probably in vivo. These cells may act as reservoirs of virus in bone marrow, brain, and other tissues. As an approach to the pathobiology of HTLV-III/LAV in hematopoiesis, several in vitro systems have been established: (a) retroviral infection of normal human peripheral, bone marrow and tissue monocyte- macrophages. The infection of these cells appears nonproductive, with virus replication demonstrable after addition of allogeneic peripheral blood mononuclear leukocytes; (b) productive retroviral infection of macrophage-like cell line, U-937; (c) suppression of marrow progenitors CFU-GM and BFU-E by HTLV-III/LAV seropositive sera but not preimmune sera. The objectives of this proposal are: (1) to characterize the nature of in vitro HTLV- III/LAV infection of bone marrow progenitor cells and macrophages; (2) to study bone marrow development after HTLV- III/LAV Infection in response to CSFs, erythropoietin and suppressive serum factors; (3) to modify in vitro HTLV-III/LAV infection of bone marrow and macrophages by treatment with cytokines or antiviral agents; (4) to examine the effects of treatment with cytokines or antiviral agents on persistent infection of U-937 cells; (5) to determine if viral variants with particular tropism for hematopoietic cells can be identified; (6) to study the protective effects of anti-HTLV-III/LAV neutralizing antibodies on infection of hematopoietic cells. These studies should increase our knowledge of regulation of hematopoiesis, and provide a framework for prophylaxis and clinical treatment of certain hematopoietic disorders.